Breast cancer is the most frequently diagnosed type of cancer in women, with 1.3 million new diagnoses and 465,000 deaths annually worldwide. There is an acute need for improved prognostic and predictive tools to aid individualized treatment for breast cancer. Tests are specifically required to identify high risk patients requiring aggressive therapy and monitoring, low risk patients who may be spared unnecessary chemotherapy, and to select specific therapies to which individuals are likely to respond. Such tests are critical to improve disease management and survival rates for breast cancer patients. The long term objective of the project is to develop and commercialize a tissue-based multiplexed immunofluorescence biomarker test for breast cancer to predict clinical outcome and responses to therapies with higher sensitivity and specificity than current diagnostic tools. An optimal panel of biomarkers will be determined using the Tissue Systeumors that can be reduced to decision "indices" with the aid of classifiers constructed from retrospective studies. In Phase I the project specifically aims to retrospectively evaluate a panel of 24 prognostic and predictive functional biomarkers by multiplexed immunofluorescence staining on tissue microarrays of breast tumor tissues from patients with good outcome and patients with poor outcome. Precise intracellular measurements of the biomarkers will be made by quantitative analysis of images generated by fluorescence digital imaging pathology. The biomarker measurements will be correlated with clinical and pathological data to determine an optimal panel of functional biomarkers. Classifier software will be built using the optimal biomarker panel to predict recurrence risk, survival and clinical outcome. The classifier will be the critical solution to convert the complex biomarker data to meaningful indices for prognostic purposes. In the Phase II of the project the utility, speciest as an addition to thecurrent IHC measurements performed at diagnosis tumor tissue sections. Successful development of the test will enable more accurate prognoses and predictions for individualized decision-making and improved disease management for breast cancer. PUBLIC HEALTH RELEVANCE: There is an acute need for improved prognostic and predictive tests to aid individualized management for breast cancer. The proposed research aims to develop a Tissue Systems Biology (CSBTM) profiling test that measures a combination of the key functions of tumors including, the immune system, that control tumor spread and the responses of tumors to cancer therapies. The test will enable more accurate prognoses and predictions of responses to therapies for individual breast cancer patients to improve management of the disease. 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